Subacute toxicity of paraquat in beagle dogs: clinicopathology and pathologic examinations

Beagle dogs were allocated to 4 groups, each consisting of 3 males and 3 females, which received 0.055, 0.165 or 0.495 mg paraquat (PQ)/kg/day sc for 4 w to investigate subacute toxicity. Recovery 4 and 8 w postadministration was studied. In the early stage there was vomiting, decreased activity and undernourishment. Induration and ulcers at the injection sites were seen. The group receiving 0.495 mg PQ/kg had reduced food ingestion and occasional decreases in water consumption until the end of the 4-w injection period. Three animals in the 0.495 mg PQ/kg group were sacrificed in the moribund stage with marked decreases in body weight. Ophthalmologic examination at 4 w of recovery detected hemorrhage around the nasalis vein of the left fundus in 1 animal that received 0.495 mg PQ/kg. No abnormal changes in electrocardiography (ECG) were noted throughout the experimental period. Slightly increased urinary protein, reticulocyte counts, and fibrinogen were observed in a few animals in each group. A few animals that received 0.165 or 0.495 mg PQ/kg had increased phospholipid, blood urea nitrogen, and creatine phosphokinase. The lungs of the moribundly sacrificed animals had moderate atelectasis, localized atelectasis, moderate thickening of alveolar wall and pleura, proliferation of fibroblast-like cells, and abundant fibers in interstitium and alveoli. In the liver there was slight hemorrhage along the gallbladder. On electron microscopy of the lung, proliferation of fibroblasts, myofibroblasts and type II alveolar cells, and some mast cells were observed in thickened alveolar walls. Abundant collagen fibers, destroyed cell debris and mitotic figures of spindle-shaped fibroblasts were also observed in the dilated interstitium.(ABSTRACT TRUNCATED AT 250 WORDS)